Abstract

Inflammatory cells play a key role in cancer and macrophages have been associated with invasion and metastasis. Tumor associated macrophage (TAM) density has been associated with poor prognosis in many cancers including breast cancer. In this study, we investigated the role of a subset of macrophages known as proliferating macrophages (promacs) in breast tumor progression. We also investigated relationship between promacs and clinical factors such as tumor size, grade, subtype, lymph node metastasis, ethnicity, and survival. We then examined the correlation between promacs, vascular endothelial growth factor A (VEGFA), and microvessel density (MVD). Tissue microarrays were constructed from paraffin embedded tissue and immunohistochemistry was performed using appropriate antibodies. The number of infiltrating promacs was found to be higher in DCIS, invasive and lymph node metastatic tissue when compared to normal breast tissue (p=0.007, 0.004, and 0.002 respectively). Higher number of promacs was also found to be significantly correlated with higher grade tumors, HER2+/ER- and basal-like subtypes, and decreased survival (p<0.001, p=0.014, and 0.009 respectively). However, no correlation was found between promacs and VEGFA (p=0.43) or promacs and MVD (p=0.24). These findings suggest that promacs play a role in the switch from normal breast tissue to cancer, that higher promacs can serve as a prognostic indicator for bad outcomes, and that the effects of promacs are not mediated through an angiogenic pathway.